Use of low molecular weight amino alcohols in opthalmic compositions

ABSTRACT

The use of low molecular weight amino alcohols in ophthalmic compositions is described. These compounds have been found to enhance the efficacy of anti-microbial preservatives.

[0001] The present application is a continuation of a 371 application,Ser. No. 09/308,456 filed May 14, 1999, which claims benefits toPCT/US97/20826 filed Nov. 17, 1997, and Provisional Application No.60/033,079 filed Dec. 13, 1996.

BACKGROUND OF THE INVENTION

[0002] The present invention relates to the field of ophthalmology. Morespecifically, the invention relates to the use of low molecular weightamino alcohols in products for treating contact lenses, as well as otherophthalmic products. The amino alcohols described herein have been foundto be useful in preserving ophthalmic compositions. The amino alcoholshave also been found to be useful in enhancing the activity ofanti-microbial preservatives, and have been found to be particularlyeffective when combined with borate or borate/polyol buffer systems.

[0003] Ophthalmic compositions generally must include an anti-microbialagent to prevent contamination of the compositions by bacteria, fungiand other microbes. Such compositions may come into contact with thecornea either directly or indirectly. The cornea is particularlysensitive to exogenous chemical agents. Consequently, in order tominimize the potential for harmful effects on the cornea, it isnecessary to use anti-microbial agents which are relatively non-toxic tothe cornea, and to use such agents at the lowest possible concentrations(i.e., the minimum amounts required in order to perform theiranti-microbial functions). This balancing of the anti-microbial efficacyand potential toxicological activity of anti-microbial agents issometimes difficult to achieve. More specifically, the anti-microbialagent concentration necessary for useful preservation of ophthalmicformation or disinfection of contact lenses may create the potential fortoxicological effects on the cornea and/or other ophthalmic tissues.Using lower concentrations of the anti-microbial agents generally helpsto reduce the potential for such toxicological effects, but the lowerconcentrations may be less effective for biocidal efficacy of ophthalmiccompositions. This weaker activity may create the potential formicrobial contamination of the compositions and ophthalmic infectionsresulting from such contaminations. This is also a serious problem,since ophthalmic infections involving pseudomonas aeruginosa or othervirulent microorganisms can lead to loss of visual function or even lossof the eye. Thus, there is a need for a means of enhancing the activityof anti- microbial agents so that very low concentrations of theseagents can be utilized without increasing the potential fortoxicological effects or increasing the risk of microbial contaminationand resulting ophthalmic infections.

[0004] Numerous anti-microbial agents have been used or suggested in theart for preserving ophthalmic compositions or disinfecting contactlenses. Such agents have included:

[0005] benzalkonium chloride (BAC), thimerosal, chlorhexidine, polymericbiguanides, such as polyhexylmethyl biguanides (PHMB), and polymericquaternary ammonium agents, such as polyquatemium-1. Other agents haveincluded alkylamines, such as the amidoamines described in U.S. Pat.Nos. 5,393,491 (Dassanayake et al.) and 5,573,776 (Dassanayake et al.).While all of these agents have offered some level of utility, their usehas also led to certain limitations or drawbacks. For example,thimerosal, which contains mercury, has caused severe ocular irritationresulting from contact lens disinfecting; BAC tends to complex in adetrimental way with negative ionic species typical in ophthalmiccompositions and the polymeric biguanides and quaternary ammoniumagents, although less ophthalmically irritating/toxic, have limitedanti-microbial efficacy against certain species of fungi, includingAspergillus fumigatus and Aspergillus niger. Furthermore, new FDAdisinfecting requirements are now being implemented which require even agreater magnitude of microbial kill against a greater number ofmicroorganisms. Thus, a need exists for enhancing the effectiveness ofthese otherwise useful anti-microbial agents.

[0006] Compositions for treating contact lenses and other types ofophthalmic compositions are generally formulated as isotonic, bufferedsolutions. One approach to enhancing the anti-microbial activity of suchcompositions is to include multi-functional components in thecompositions. In addition to performing their primary functions, such ascleaning or wetting contact lens surfaces (e.g., surfactants), bufferingthe compositions (e.g., borate), or chelating undesirable ions (e.g.,EDTA), these multi-functional components also serve to enhance theoverall anti-microbial activity of the compositions. For example,ethylenediaminetetraacetic acid and the monosodium, disodium andtrisodium salts thereof (collectively referred to herein as “EDTA”) hasbeen widely used for many years in ophthalmic products, particularlyproducts for treating contact lenses. It has been used in such productsfor various purposes, but particularly for its supplementalanti-microbial activity and as a chelating agent. The inclusion of EDTAin contact lens care products and other ophthalmic compositions enhancesthe anti-microbial efficacy of chemical preservatives contained in suchcompositions, particularly the efficacy of those preservatives againstgram negative bacteria.

[0007] Borate buffer systems are used in various types of ophthalmiccompositions. For example, two commercial solutions for disinfectingcontact lenses, OPTI-SOFT® (0.001% polyquaternium-1) DisinfectingSolution marketed by Alcon Laboratories, Inc. and ReNu® Multi-PurposeSolution (0.00005% polyhexamethylene biguanide) marketed by Bausch &Lomb, Inc., contain borate buffer systems which contribute to thedisinfecting efficacy of the solutions. An improved borate buffer systemfor ophthalmic compositions is described in U.S. Pat. Nos. 5,342,620(Chowhan) and 5,505,953 (Chowhan). That system utilizes borate incombination with one or more polyols, such as mannitol. This combinationenhances the anti-microbial activity of compositions, beyond theenhancement obtained with borate alone. However, the present inventorshave found that the water soluble complex formed by the borate/polyolalso reduces the pH of compositions significantly. As a result ofefforts directed to solving this and other problems, the presentinventors have discovered that certain amino alcohols can be effectivelyand safely utilized to provide pH-buffering of ophthalmic compositionsand to further enhance the anti-microbial activity of the compositions.

[0008] The use of tromethamine in compositions and methods fordisinfecting contact lenses is described in U.S. Pat. No. 5,422,073(Mowrey-McKee, et al.). This publication indicates that a synergisticeffect is obtained when tromethamine is combined with other knownmicrobicides and chelating agents. EDTA is identified as the preferredchelating agent.

[0009] In view of the foregoing, there is a need for an improved meansfor enhancing the activity of anti-microbial agents so as to preserveophthalmic compositions from microbial contamination and disinfectcontact lenses more efficaciously. The present invention is directed tosatisfying this need.

SUMMARY OF THE INVENTION

[0010] The present invention is based on a new use of a specific groupof low molecular weight amino alcohols. The present inventors have foundthat the amino alcohols described herein enhance the activity ofanti-microbial agents, particularly when utilized in combination withborate or borate/polyol buffer systems. The enhancement is more thanadditive. Thus, although the mechanisms of action are not fullyunderstood, it is believed that the low molecular weight amino alcoholsof the present invention produce a synergistic enhancement ofanti-microbial activity.

[0011] The present inventors have also found that the subject aminoalcohols are very effective in neutralizing the acid pH of borate/polyolcomplexes. This buffering effect of the amino alcohols is significant.Although conventional bases, such as sodium hydroxide, may be utilizedto adjust the pH of acidic solutions containing borate/polyol complexes,the amino alcohols described herein have a significantly higherbuffering capacity. This enhanced buffering capacity is particularlyimportant if the compositions contain anti-microbial agents which are pHdependent (e.g., alkyl amidoamines). If the pH of such compositions isnot maintained within the range required for maximum anti-microbialactivity, the overall anti- microbial activity of the composition may bereduced. The use of borate-polyol buffering system may alsosignificantly reduce the amount of NaOH necessary for pH adjustments,and therefore reduce the amount of ions in the compositions. Thisfeature is particularly significant when ion sensitive anti-microbialagents, such as polyquatemium-1, are employed.

[0012] The amino alcohols may be used in various types of ophthalmiccompositions, particularly compositions for treating contact lenses,such as disinfectants, cleaners, comfort drops and rewetting drops. Thelow molecular weight amino alcohols are particularly useful incompositions for disinfecting, rinsing, storing and/or cleaning contactlenses. When these compounds are combined with borate buffer systems,the combination also helps to preserve the products against microbialcontamination. This anti-microbial effect of the amino alcohol/boratecombination reduces the amount of anti-microbial agent required forpreservative purposes, and in some instances, may totally eliminate theneed for a conventional anti-microbial preservative agent.

[0013] The present invention is particularly directed to the provisionof improved compositions for disinfecting contact lenses. Thecompositions have significantly enhanced anti-microbial activity,relative to prior compositions containing the same primary disinfectingagents (e.g., polyquaternium-1). The enhancement is achieved by means ofa combination of formulation criteria, including the use of aborate/polyol complex and one or more amino alcohols, as describedherein. This enhancement of anti-microbial activity is highlysignificant. Preferred disinfecting compositions also contain arelatively small amount of an alkylamine. New government regulations insome countries have, in effect, created a need for compositions havingsignificantly greater anti-microbial activity. More specifically, thenew regulations require that compositions for disinfecting contactlenses be capable of achieving disinfection without assistance fromother compositions (e.g., cleaning compositions or preserved salinerinsing solutions). The enhancement of anti-microbial activity achievedby means of the present invention enables contact lens disinfectingcompositions to satisfy this standard.

DETAILED DESCRIPTION OF THE INVENTION

[0014] The low molecular weight amino alcohols which may be utilized inthe present invention are water soluble and have a molecular weight inthe range of from about 60 to about 200. The following compounds arerepresentative of the low molecular weight amino alcohols which may beutilized in the present invention: 2-Amino-2-methyl-1-propanol (AMP), 2-dimethylamino-methyl-1-propanediol (DMAMP),2-amino-2-ethyl-1,3-propanediol (AEPD), 2-amino-2-methyl-1,3-propanediol (AMPD), 2-amino-1-butanol (AB). “AMP-95,”which refers to 95% pure AMP and 5% water, is the most preferred lowmolecular weight amino alcohol of the present invention. These aminoalcohols are available commercially from Angus Chemical Company (BuffaloGrove, Illinois).

[0015] The amount of amino alcohol used will depend on the molecularweight of the amino alcohol selected, the other ingredients in thecomposition, i.e., other anti-microbial agents, chelating agents,buffering agents, tonicity agents, and the function of theanti-microbial agents contained in the ophthalmic compositions (i.e.,preservation of compositions or disinfection of contact lenses). Ingeneral, one or more of the above-described amino alcohols will beutilized in a concentration of from about 0.01 to about 2.0 percent byweight/volume (“%w/v”), and preferably from 0.1 to 1.0% w/v. Whenborate/polyol complexes are employed with the amino alcohol compositionsof the present invention, the amino alcohols will generally be presentin an amount necessary to neutralize the pH of the complex, or bring thecomposition to a desired pH. This amount, therefore, is a function ofthe particular borate/polyol mixture and concentration.

[0016] The low molecular weight amino alcohols described herein may beincluded in various types of ophthalmic compositions to enhanceanti-microbial activity, or for the other purposes mentioned above.Examples of such compositions include: ophthalmic pharmaceuticalcompositions, such as topical compositions used in the treatment ofglaucoma, infections, allergies or inflammation; compositions fortreating contact lenses, such as cleaning products and products forenhancing the ocular comfort of patients wearing contact lenses; andvarious other types of compositions, such as ocular lubricatingproducts, artificial tears, astringents, and so on. The compositions maybe aqueous or non-aqueous, but will generally be aqueous.

[0017] In addition to the low molecular weight amino alcohols describedabove, the compositions of the present invention may contain one or moreanti-microbial agents to preserve the compositions from microbialcontamination and/or disinfect contact lenses. For example, thecompositions may contain the anti-microbial agent known aspolyquaternium- 1 or POLYQUAD® (registered trademark of AlconLaboratories, Inc.); the use of this agent as a preservative inophthalmic compositions is described in U.S. Pat. No. 4,525,346 (Stark).The entire contents of the Stark '346 patent are hereby incorporated inthe present specification by reference. Additional examples ofanti-microbial agents include chlorhexidine, alexidine, hexetidine,polyhexamethylene biguanide, benzalkonium chloride, benzododecinumbromide, alkylamines, alkyl di-, tri-amine and other anti-microbialagents utilized as anti-microbial preservatives or disinfecting agentsin ophthalmic compositions. The inclusion of one or more of theabove-described low molecular weight amino alcohols in ophthalmiccompositions containing such anti-microbial agents enhances the overallanti- microbial activity of the compositions. This enhancement isparticularly evident when the compositions include a borate orborate-polyol buffer system.

[0018] As indicated above, the low molecular weight amino alcoholsdescribed above are preferably used in combination with borate orborate/polyol buffer systems. As used herein, the term borate shallrefer to boric acid, salts of boric acid and other pharmaceuticallyacceptable borates, or combinations thereof. The following borates areparticularly preferred: boric acid, sodium borate, potassium borate,calcium borate, magnesium borate, manganese borate, and other suchborate salts. As used herein, and unless otherwise indicated, the termpolyol shall refer to any compound having at least two adjacent -OHgroups which are not in trans configuration relative to each other. Thepolyols can be linear or cyclic, substituted or unsubstituted, ormixtures thereof, so long as the resultant complex is water soluble andpharmaceutically acceptable. Examples of such compounds include: sugars,sugar alcohols, sugar acids and uronic acids. Preferred polyols aresugars, sugar alcohols and sugar acids, including, but not limited to:mannitol, glycerin, xylital and sorbitol. Especially preferred polyolsare mannitol and sorbitol; most preferred is sorbitol. The use ofborate-polyol complexes in ophthalmic compositions is described incommonly assigned U.S. Pat. Nos. 5,342,620 (Chowhan) and 5,505,953(Chowhan); the entire contents of which are hereby incorporated in thepresent specification by reference. The compositions of the presentinvention preferably contain one or more borates in an amount of fromabout 0.01 to about 2.0% w/v, more preferably from about 0.3 to 1.2%w/v, and one or more polyols in an amount of from about 0.01 to 5.0%w/v, more preferably from about 0.6 to 2.0% w/v.

[0019] As stated above, current disinfecting compositions are unable tomeet the new FDA requirements for disinfecting efficacy of contact lensdisinfecting compositions. The compositions of the present inventionimprove on these prior art compositions with the inclusion of aminoalcohols in the compositions. The most preferred contact lensdisinfecting compositions of the present invention comprise one or morelow molecular weight amino alcohol(s), a borate-polyol buffer, ananti-microbial agent, as described above, and an alkylamine.

[0020] Alkylamines have been described in commonly owned U.S. Pat. Nos.5,393,491 (Dassanayake et al.), and 5,573,726 (Dassanayake et al.), andU.S. patent application Serial No. 08/381,889. The foregoing patents andpatent application are hereby incorporated in the present specificationby reference. These alkylamines possess both anti-bacterial andanti-fungal activity. Preferred alkylamines are the amidoamines, asdescribed in the above-referenced Dassanayake et al. patents. The mostpreferred amidoamine is myristamidopropyldimethyl-amine (“MAPDA”).

[0021] The amount of alkylamine in the compositions of the presentinvention will vary, due to various factors such as: anti-microbialpotency and potential toxicity of the particular alkylamine. The presentinventors have found, however, that the amount of alkylamines,particularly the amidoamines, useful in the compositions of the presentinvention is dramatically lower when combined with compositionscomprising borate buffers, than when the alkylamines are employedwithout borates. Generally, the alkylamines will be present inconcentrations of from about 0.00005 to about 0.01% w/v, when combinedwith borates.

[0022] As will be appreciated by those skilled in the art, thepreserving or disinfecting compositions may also contain a wide varietyof other ingredients, such as tonicity agents (e.g., sodium chloride ormannitol), surfactants (e.g., alkyl ethoxylates andpolyoxyethylene/polyoxypropylene copolymers), and viscosity adjustingagents. The present invention is not limited with respect to the typesof ophthalmic compositions in which the other low molecular weight aminoalcohols described above are utilized.

[0023] All of the above-described compositions will be formulated so asto be compatible with the eye and/or contact lenses to be treated withthe compositions. As will be appreciated by those skilled in the art,the ophthalmic compositions intended for direct application to the eyewill be formulated so as to have a pH and tonicity which are compatiblewith the eye. This will normally require a buffer to maintain the pH ofthe composition at or near physiologic pH (i.e., 7.4) and may require atonicity agent to bring the osmolality of the composition to a level ator near 210-320 milliosmoles per kilogram (mOsm/kg). The formulation ofcompositions for disinfecting and/or cleaning contact lenses willinvolve similar considerations, as well as considerations relating tothe physical effect of the compositions on contact lens materials andthe potential for binding or absorption of the components of thecomposition by the lens.

[0024] The following examples are presented to further illustrateselected embodiments of the present invention.

Example 1

[0025] The following saline solutions containing various amino alcoholsat a concentration of 1.2% were prepared for comparative purposes. Thecomposition of the solutions is presented below. The pH of the solutionswas adjusted to 7.4 with hydrochloric acid. The amino alcohols consistedof 2-Amino-2-methyl-1-propanol (AMP), 2-dimethylamino-methyl-1-propanediol (DMAMP), 2-amino-2-ethyl-1,3-propanediol (AEPD),2-amino-2-methyl-1,3- propanediol (AMPD), and1,4-Bis(2-hydroxyethyl)-piperazine (BHP). The osmolalities of thesolutions were 335, 250, 254, 304 and 208 mOsm/kg, respectively.Ingredients Amount (w/v %) Amino Alcohol 1.2% Sodium Chloride 0.3%Disodium Edetate 0.05%  Purified Water QS

[0026] The antibacterial activity of the above-described salinesolutions against S. marcescens was evaluated. The formulations wereevaluated by inoculating 20 ml of each solution with 0.1 ml of amicrobial suspension. The final concentration was 10⁶ colony formingunits (“CFUs”) per ml. At each time point, pour plates of SCDA wereprepared containing diluted aliquots of the various test samples. Thebacteria and yeast plates were incubated at 30° to 35° C. for 2 to 3days. The mold plates were incubated at 20° to 25° C for five days.Following the colony incubation period, the number of CFUs were countedand the log reduction of the CFUs relative to the starting amount wascalculated.

[0027] The results at 6 and 24 hours (in log reduction of survivors) areshown in Table 1 below: TABLE 1 Log Reduction of Survivors Amino Alcohol6 hours 24 hours AMP 0.1 0.5 DMAMP 0.0 0.7 AEPD 0.0 0.7 AMPD 0.0 0.0 BHP0.1 0.1

[0028] As indicated by the foregoing data, all of the formulationsexhibited minimal activity against S. marcescens.

Example 2

[0029] The following is an example of a preserving composition of thepresent invention (Formulation A) and a comparative composition(Formulation B). Both formulations, contain a borate/polyol buffersystem (i.e., boric acid and mannitol), but differ in that Formulation Autilizes AMP-95 and Formulation B utilizes NaOH to adjust the pH. Theformulations were prepared by first sequentially dissolving in 90 ml ofpurified water, boric acid, mannitol, poloxamine and disodium edetate.AMP-95 was added to Formulation A and the volume was adjusted to 100 mlwith purified water. The pH of Formulation A was 7.4. The pH ofFormulation B was adjusted to 7.4 with 6N NaOH, and the volume of thesolution was adjusted to 100 ml with purified water. Both formulationshad an osmolality of about 200 mOsm/kg. The compositions of the twoformulations are set forth below: Amount (w/v %) Ingredients FormulationA Formulation B Boric Acid 1.0% 1.0% Mannitol 1.5% 1.5% Disodium Edetate0.05%  0.05%  Polaxamine 0.1% 0.1% AMP-95 0.56%  — Sodium hydroxide — pHto 7.4 Purified Water QS QS

[0030] The anti-microbial activity of the formulations against S.marcescens and P. aeruginosa was evaluated. A similar microbial protocolto the Example 1 protocol was employed The results are presented inTable 2 below: TABLE 2 Microorganism Time Formulation A Formulation B S.marcescens  6 hours 0.1 0.0  24 hours 1.1 0.2 168 hours 4.5 1.5 P.aeruginosa  6 hours 5.0 1.0  24 hours 6.0 1.4

[0031] As indicated by the foregoing data, Formulation A exhibitedsignificantly greater antibacterial activity than Formulation B, whichdoes not contain an amino alcohol in accordance with the presentinvention. This example demonstrates that the effect of amino alcohol ina borate composition surpasses the anti-bacterial effect of EDTA alone(Formulation B).

Example 3

[0032] The following is a comparative example of a preserving and/ordisinfecting composition of the present invention (Formulation C) and acomparative composition (Formulation D). Two formulations similar tothose described in Example 2 above, but containing the anti-microbialagent POLYQUAD®, were prepared. The formulations were prepared by meansof procedures similar to those described in Example 2, above. POLYQUAD®was added before final pH adjustment. The pH of formulation C was 7.4;the pH of Formulation D was adjusted to pH 7.4 with 6N NaOH. Thecomposition of the formulations is presented below: Amount (w/v %)Ingredients Formulation C Formulation D Boric Acid 1.0% 1.0% Mannitol1.5% 1.5% Disodium Edetate 0.05%  0.05%  Polaxamine 0.1% 0.1% POLYQUAD ®0.0005%   0.0005%   AMP-95 0.56%  — Sodium Hydroxide — pH to 7.4Purified Water QS QS

[0033] The anti-microbial activity of the formulations against S.marcescens, S aureus and P. aeruginosa was evaluated. Microbialprotocols similar to the Example 1 protocol were employed. The resultsare presented in Table 3 below: TABLE 3 Microorganism Time Formulation CFormulation D S. marcescens  6 hours 2.9 2.4  24 hours 3.3 3.0 168 hours6.1 4.8 S. aureus  6 hours 5.1 4.4  24 hours 6.1 5.9 P. aeruginosa  6hours 6.0 5.3  24 hours 6.0 6.0

[0034] These results demonstrate that the amino alcohol contained inFormulation C significantly enhanced the anti-microbial activity of thecomposition.

Example 4

[0035] The following is a preferred multi-purpose composition for thecleaning, disinfecting, rinsing and storing of soft hydrophilic lenses:Ingredient % (w/v) Polyquaternium-1 0.001 Boric acid 0.6 Sorbitol 1.2Sodium chloride 0.1 Sodium citrate 0.65 Tetronic 1304 0.05 DisodiumEdetate 0.05 Sodium hydroxide pH 7.8 Hydrochloric acid pH 7.8 Purifiedwater QS AMP-95  0.45% MAPDA 0.0005%

[0036] The anti-microbial activity of the above composition against A.fumigatus, C. albicans, F. solani, P. aeruginosa, S. marcescens, S.aureus and S. warneri was evaluated. Microbial protocols similar to thatof Example 1 for the various microorganisms were employed. The resultsare illustrated in Table 4, below: TABLE 4 Microorganism Time (Hrs) LogReduction A.fumigatus 4 2.2 ATCC 10894 6 3.1 24 4.8 48 4.8 C. albicans 41.5 ATCC 10231 6 1.7 24 2.7 48 4.0 F. solani 4 3.8 ATCC 36031 6 4.3 245.6 48 5.8 P. aeruginosa 4 4.7 ATCC 9027 6 5.7 24 6.1 48 6.1 S.marcescens 4 3.3 ATCC 13880 6 4.1 24 6.0 48 4.7 S. marcescens 4 2.1 ATCC14041 6 2.7 24 5.6 48 5.6 S. aureus 4 3.7 ATCC 6538 6 3.7 24 5.5 48 6.1S. warneri 4 4.9 ATCC 17917 6 5.1 24 5.9 48 5.9

Example 5

[0037] The following is a comparative example of a multi-purposecomposition of the present invention (Formulation E) and a comparativecomposition (Formulation F). The two formulations are the same, exceptthat Formulation F does not contain EDTA. Formulation E Formulation FComponent Concentration (% w/v) MAPDA 0.0005 0.0005 AMP-95 0.45 0.45Boric Acid 0.6 0.6 Polyquaternium-1 0.001 0.001 Sodium Citrate 0.65 0.65Sodium Chloride 0.1 0.1 Sorbitol 1.2 1.2 Tetronic 1304 0.05 0.05Disodium EDTA 0.05 — NaOH/HCl pH 7.8 pH 7.8 Purified Water QS QS

[0038] The anti-microbial activity of the above compositions against P.aeruginosa, S. marcescens, S. aureus, and C. albicans was evaluatedusing a protocol similar to that of Example 1, above. The log reductiondata is illustrated in Table 5, below: TABLE 5 Microorganism Time (Hrs)Formulation E Formulation F P. aeruginosa 6 4.7 4.7 ATCC 9027 24 6.0 6.0S. marcescens 6 3.2 3.3 ATCC 13880 24 5.1 4.9 S. aureus 6 3.9 3.6 ATCC6538 24 4.9 6.1 C. albicans 6 1.1 1.4 ATCC 10231 24 4.3 5.1

Example 6

[0039] The following composition is an example of a multi-purposecomposition useful for cleaning, rinsing, disinfecting and conditioningRigid Gas Permeable (RGP) lenses: Component Amount Hydroxy propyl methylcellulose 0.4% Tetronic 1304 0.5% Boric Acid 0.6% Sorbitol 1.2% DisodiumEdetate 0.01%  AMP-95 0.4% Propylene glycol 0.5% Polyquaternium-10.0005%   NaOH/HCl pH 7.6 Purified water QS

[0040] The anti-microbial activity of the above composition againstagainst S. marcescens, S. aureus, and C. albicans was evaluated using aprotocol similar to that of Example 1, above. The log reduction data isillustrated in Table 6, below: TABLE 6 Log₁₀ Reduction MicroorganismTime of Survivors C. albicans 4 3.6 6 4.1 24 5.3 S. marcescens 4 3.6 62.6 24 5.5 S. aureus 4 5.1 6 4.8 24 6.1

Example 7

[0041] The following is an example of a disinfecting composition usefulfor soft hydrophilic lenses. Component Amount Boric Acid 0.1% Sorbitol0.2% AMP-95 0.07% Propylene glycol 1.4% DS EDTA 0.01% Polyquaternium-10.0001% NaOH/HCl pH 7.6 Purified water QS

[0042] The anti-microbial activity of the above composition againstagainst S. marcescens, S. aureus, and C. albicans was evaluated using aprotocol similar to that of Example 1, above.

[0043] The log reduction data is illustrated in Table 7, below: TABLE 7Log₁₀ Reduction Microorganism Time of Survivors C. albicans 6 1.5 24 3.0S. marcescens 6 4.6 24 6.2 S. aureus 6 2.7 24 5.1

What is claimed is:
 1. A method of enhancing the anti-microbial activityof an ophthalmic composition containing a borate compound whichcomprises adding to the composition an effective amount of a lowmolecular weight amino alcohol, wherein the amino alcohol has amolecular weight of from 60 to
 200. 2. A method according to claim 1,wherein the composition further comprises a borate/polyol buffer system.3. A method according to claim 1 or 2, wherein the amino alcohol isselected from the group consisting of 2-amino-2-methyl-1-propanol (AMP),2-dimethylamino-methyl-1- propanediol (DMAMP),2-amino-2-ethyl-1,3-propanediol (AEPD), 2-amino-2-methyl-1,3-propanediol (AMPD), 2-amino-1-butanol (AB).
 4. A method according toclaim 1, 2 or 3, wherein the composition further comprises analkylamine.
 5. A sterile, multi-dose ophthalmic composition comprisingan amount of a low molecular weight amino alcohol effective to enhancethe anti-microbial activity of a borate containing composition, whereinthe amino acid has a molecular weight of from 60 to
 200. 6. Acomposition according to claim 5, wherein the composition is adapted forthe treatment of contact lenses.
 7. A composition according to claim 5or 6, wherein the composition further comprises a borate/polyol buffersystem.
 8. A composition according to claim 5, 6 or 7, wherein the aminoalcohol is selected from the group consisting of 2-amino-2-methyl- 1-propanol (AMP), 2-dimethylamino-methyl-1 - propanediol (DMAMP),2-amino-2-ethyl-1,3-propanediol (AEPD), 2-amino-2-methyl-1,3-propanediol (AMPD), 2-amino-1-butanol (AB).
 9. A composition accordingto claim 5, 6, 7 or 8, further comprising an alkylamine.
 10. Acomposition according to claim 5, 6, 7, 8 or 9, wherein the alkylamineis an amidoamine.
 11. A composition according to claims 5 to 10, whereinthe composition is a multi-purpose composition comprising:polyquaternium-1, boric acid, sorbitol, sodium chloride, sodium citrate,Tetronic 1304, disodium edetate, sodium hydroxide, hydrochloric acid,purified water, 2-amino 2-methyl propanol and MAPDA.
 12. A compositionaccording to claims 5 to 11, wherein the composition further comprises:about 0.001% w/v of polyquatemium-1; about 0.6% w/v of boric acid; about1.2% w/v of sorbitol; about 0.65% w/v of sodium citrate; about 0.1% w/vof sodium chloride; about 0.05% w/v of Tetronic 1304; about 0.05% w/v ofdisodium edetate; about 0.45% w/v of AMP-95; about 0.0005% w/v of MAPDA;and wherein the composition is adjusted to pH 7.8 with sodium hydroxideand hydrochloric acid.